Oxatomide, sold under the brand name Tinset among others, is a first-generation antihistamine of the

diphenylmethylpiperazine 1-(Diphenylmethyl)piperazine, also known as benzhydrylpiperazine, is a chemical compound and piperazine derivative. It features a piperazine ring with a benzhydryl (diphenyl methyl) group bound to one of the nitrogen Nitrogen is the chemical ...

family which is marketed in Europe,

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

, and a number of other countries. It was discovered at Janssen Pharmaceutica in 1975. Oxatomide lacks any anticholinergic effects. In addition to its H₁ receptor antagonism, it also possesses

antiserotonergic A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action at serotonin (5-HT) receptors. Types 5-HT2A antagonists Antagonists of the 5-HT2A receptor are sometimes used as atypical antipsychotics (contrast wi ...

activity similarly to hydroxyzine. It was patented in 1976 and came into medical use in 1981.

Chemistry

Synthesis

Reaction of 2-Benzimidazolinone with

isopropenyl acetate Isopropenyl acetate is an organic compound, which is the acetate ester of the enol tautomer of acetone. This colorless liquid is significant commercially as the principal precursor to acetylacetone. In organic synthesis, it is used to prepare en ...

leads to the singly protected imidazolone derivative (2). Alkylation of this with 3-chloro-1-bromopropane affords the functionalized derivative (3). Alkylation of the monobenzhydryl derivative of piperazine (4) with 3 gives oxatomide (5), after hydrolytic removal of the

protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In many ...

References

Benzimidazoles Belgian inventions H1 receptor antagonists Janssen Pharmaceutica Gamma-lactams Cyclizines Ureas {{Respiratory-system-drug-stub